This phase II trial studies how well cabozantinib-s-malate works in treating patients with endometrial cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Patients receive cabozantinib-s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malate

Given PO

Other Names:

BMS-907351

Cabometyx

Cometriq

XL184

Other: Laboratory Biomarker Analysis

Correlative studies

Other: Pharmacological Study

Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine efficacy of single agent cabozantinib in women previously receiving one line of chemotherapy for metastatic endometrial cancer or with progression within 12 months of completing adjuvant therapy, with co-primary endpoints of objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and progression-free-survival at 12 weeks (PFS).

Patients receive cabozantinib-s-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must have histologically or cytologically confirmed metastatic endometrial cancer; eligible histologies for the experimental cohort are: endometrioid or serous; eligible histologies for the exploratory cohort are: carcinosarcoma, clear cell, mixed, adenosquamous and any other rare sub-type of endometrial cancer

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam and >= 15 mm in short axis for nodal lesions; patients must have radiographic evidence of disease progression following the most recent line of treatment

Prior therapy: Eligible subjects must have had 1 line of systemic cytotoxic treatment; this may be adjuvant therapy with documented progression within 12 months of completion, or 1 line of cytotoxic therapy for metastatic disease; prior hormonal therapy for metastatic/recurrent disease is also allowed; prior targeted therapy not directed against cMET or vascular endothelial growth factor (VEGF) pathways is allowed

Women of childbearing potential must have a negative pregnancy test at screening; women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopausal is defined as amenorrhea >= 12 consecutive months; note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason

Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; sexually active subjects must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s)

Patients must consent to analysis on archival tissue; if archival sample is not available, a sufficient tumor biopsy can be performed a minimum of 28 days prior to start of treatment if felt to be clinically reasonable

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Patients who have had chemotherapy (including investigational cytotoxic chemotherapy), biologic agents (e.g., cytokines or antibodies) or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before the first dose of study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

Prior treatment with cabozantinib

The subject has received radiation therapy:

To bone metastasis within 14 days before the first dose of study treatment

To any other site(s) within 28 days before the first dose of study treatment

The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment

The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment

The subject has received any other type of investigational agent within 28 days before the first dose of study treatment

The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from related toxicity to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)

Any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other cancer

Patients with known brain metastases should be excluded from this clinical trial

The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test >= 1.3 x the laboratory ULN =< 7 days before the first dose of study treatment

Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment

Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment

Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment

The subject has tumor in contact with, invading or encasing any major blood vessels

The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib

The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

Cardiovascular disorders including:

Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening

Any of the following within 6 months before the first dose of study treatment:

Abdominal fistula

Gastrointestinal perforation

Bowel obstruction or gastric outlet obstruction

Intra-abdominal abscess; note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment

Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy

Other clinically significant disorders such as:

Active uncontrolled infection requiring intravenous systemic treatment within 14 days before the first dose of study treatment

Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment

History of organ transplant

Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment

History of major surgery as follows:

Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications

Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications

In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery

The subject is unable to swallow tablets

The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms =< 7 days before the first dose of study treatment

The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

History of allergic reactions attributed to compounds of similar chemical or biologic composition to XL184

Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with XL184

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01935934